Rheumatoid

Arthritis
Prof. Samah Ismail Nasef
MD, MRCP Rheumatology UK
Professor of Rheumatology & Rehabilitation
Agenda
• Case presentation
• History
• Examination
• Investigations
• Summary
• Diagnosis

• Discussion

• Questions
History
• Hanan is a 30-year-old woman
presented with joint pain in both
hands, wrists, elbows, and
ankles.
• She had been having
intermittent symptoms over 3
years and had been taking
ibuprofen with some relief of
the symptoms.
• Six months prior to this
presentation she reports
having constant joint pain and
swelling with impairment in
function and daily activities.
She also complained of fatigue
and decreased appetite.

• She had morning stiffness

lasting about 2–3 hours.
Review of systems
• She denied photosensitivity, colour changes in fingers and
toes, mouth ulcers, chest pain, or difficulty breathing.

• She reported dryness in her eyes and mouth.

• She had mild epigastric discomfort with Ibuprofen.

• Denied bleeding disorders, diarrhoea, or constipation.

• No history of psoriasis, gout, or skin conditions.

• She denied night sweats, chills, or weight loss.

Past medical history
• She had no other medical conditions,
denied having any drug or food allergies,
and never had surgeries or hospital
admissions.
Family history
• Significant for diabetes in mother.

• Denied having first-degree relatives with

rheumatoid arthritis, SLE, or other
autoimmune disease.
• From the history, what
is your differential
diagnosis?

• Is there anything
missing at this history?
Physical examination
• She was well appearing; vital
signs were within normal
limits.

• Head and neck exam: No

butterfly rash, no mouth
ulcers, no lymphadenopathy.

• Eye exam revealed

erythematous injection of
the conjunctiva bilaterally,
no discharge.
• Cardiovascular and pulmonary
examination was normal.

• Abdominal exam was positive for mild

mid-epigastric tenderness.

• No hepatosplenomegaly
Musculoskeletal examination
• Swelling and tenderness in
4th and 5th MCP and PIP
joints bilaterally.

• tenderness without swelling

in 2nd, 3rd MCPs bilaterally.

• Both wrist and elbow joints

were tender with appreciable
warmth.

• Shoulders without pain and

had full range of motion.
Musculoskeletal examination
• Lower extremity exam
showed no pain with range of
motion in the hips, knees,
and ankles. These joints were
without effusions or warmth.

• She had tenderness on

palpation of MTP joints with
positive MTP squeeze test.
• Skin: No rash, psoriatic plaques, nodules,
tophi.

• Neurologic examination showed normal

strength and sensation.

• The remainder of her examination was

normal.
 Discriminating Inflammatory from Non-Inflammatory Arthritis 1

Feature Inflammatory Non-inflammatory

Joint pain With activity and at rest With activity

Joint swelling Soft tissue Bony

Local erythema Sometimes Absent

Local warmth Frequent Absent

Morning stiffness >30 minutes <30 minutes

Systemic symptoms Common, especially fatigue Absent

System Features That May Suggest Alternative Diagnosis

System Feature
• Mucosal ulcers
• Photosensitivity
Skin • Skin rashes
• Psoriasis

Eye • Iritis/uveitis

• Inflammatory bowel disease

Bowel • Infectious diarrhea

• Raynaud’s
• Urethritis
Other • Isolated distal interphalangeal joint inflammation
• Nephritis
• Myositis
Laboratory findings

• Which laboratory
investigations you
need to order for this
lady to reach final
diagnosis?
Laboratory findings
Test Patient value Reference range

• WBC (K/UL) 6.3 4.0–11.0

• HGB (g/dL) 11.7 L 11.8–16
• HCT (%) 35.5 L 36.0–37
• MCV 86 80–97
• Platelet (K/UL) 262 150–400

• ALT (U/GL) 20 9.0–67.0

• AST (U/GL) 22 13–39
• BUN (mg/dL) 10 7–25
• Creatinine (mg/dL) 0.64 0.5–1.1
Laboratory findings
• Test Patient value Reference range

• ESR (mm/h) 12 0–20

• CRP (mg/dL) 29 H 0–5
• Rheumatoid factor (IU/mL) 32 H <30
• HEP B surface AB Nonreactive Non-reactive
• HEP B surface AG Nonreactive Non-reactive
• HEP C antibody Nonreactive Non-reactive
• Are there any other
laboratory
investigations to
support your
diagnosis?

• What are other

investigations?
Diagnostic Laboratory and Imaging Tests for
Evaluation of RA
Test Result
• Positive RF is not diagnostic of RA (can be seen in conditions other
RF1,2 than RA*)
• Incidence of positivity increases with duration of disease (i.e., 6-12
months) and with age
• Elevated ESR and/or CRP may present at diagnosis (elevated levels
ESR or CRP 1
reflect systemic inflammation; no well-defined cut-off points to
indicate disease activity)

• Positivity is associated with the development of bony erosions and

radiographic progression of disease†
ACCP1,2,3
• Sensitivity increases when used in combination with RF
• Very low false positive rate (<3%), even in patients with early disease

• Useful option when diagnosis is uncertain

Arthrocentesis2 • Fluid is usually straw-coloured and fibrin flecks are often seen
(joint aspiration) • A white blood cell count of 5 to 25, 000 per mm3 is common, with a
differential count of 85% polymorphonuclear leukocytes

• Depending on disease severity, radiography can reveal soft tissue

*Other conditions include other rheumatic diseases, infections, malignancies and in healthy individuals; †Independent of RF presence.
Plain Film Radiography 1,2
ACCP: anti-cyclic citrullinated swelling and joint space narrowing as a consequence of cartilage
peptide; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; RA: rheumatoid arthritis; RF: rheumatoid factor.

thinning, or joint space widening as an indication of joint effusion,

1. Littlejohn EA and Monrad SU. Prim Care 2018;45:237-255; 2. Birch JT Jr and Bhattacharya S. Prim Care 2010;37:779-792; 3. Barra et al. 2011;50:311-316.

and juxta-articular osteoporosis

 X-rays of the hands in this case showed significant narrowing of the
radiocarpal joints bilaterally (A), with narrowing of carpal (B) and
metacarpal–phalangeal joints (C). Narrowing of the second and third PIP
joints (D). Erosions are seen within carpal bones (E). No evidence of
subluxation.
Summary
• A 30-year-old woman who presented with 3 years of
progressive joint symptoms, associated with morning stiffness
and fatigue.
• She has inflammatory arthritis on exam and ocular findings.
• In addition, basic laboratory testing revealed mild anaemia,
• elevated CRP and normal renal and liver function tests.
• She had X- ray changes of both hands.
• This clinical presentation was highly suspicious for rheumatoid
arthritis.
This clinical
presentation was
highly suspicious for
rheumatoid arthritis
with …….??
Discussion
• Rheumatoid arthritis is the most common inflammatory
arthritis, with a lifetime prevalence of up to 1% worldwide.
• Onset can occur at any age, but peaks between 30 and 50
years.
• Use of tobacco, female gender, and family history of the
disease are all risk factors for RA
• A patient with joint pain and with physical exam findings of
synovitis should be evaluated for rheumatoid arthritis
including testing for RF, anti-CCP antibodies, and inflammatory
markers.
• Early diagnosis of rheumatoid arthritis is critical, so that
appropriate treatment can be administered.
2010 ACR/EULAR Classification Criteria for RA
Joint involvement One large joint 0
2-10 large joints 1
1-3 small joints* 2
4-10 small joints* 3
>10 joints (at least one small joint) 5
Serology# RF- and ACPA- 0
Low RF+ or low ACPA+ 2
High RF+ or high ACPA+ 3
Acute-phase reactants# Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
Duration of symptoms <6 weeks 0
≥6 weeks 1

Synovitis plus score of ≥6/10 needed for the classification of definite RA

*With or without involvement of large joints.
#
At least one test result needed for classification.

Adapted from Aletaha et al. Ann Rheum Dis 2010;69:1580-8.

 2010 ACR/EULAR Classification Criteria for RA

• Joint involvement:
• Any joint with swelling or tenderness on examination that is indicative of active
synovitis.
• Tenderness is included as an equally important feature as swelling for the
determination of joint involvement.
• Any joints with known recent injury that could contribute to swelling or
tenderness should not be considered. Additional evidence of joint activity from
other imaging techniques (such as MRI or ultrasound) may be used for
confirmation of the clinical findings.
• Small joints: Include the MTP, proximal interphalangeal, second to
fifth MTP and thumb interphalangeal joints and the wrists. They do
not include the first CMC, first MTP, or DIP joints, which are often
affected by OA.
• large joints: Include the shoulders, elbows, hips, knees, and ankles.

DIP: Distal interphalangeal joint; MTP: Metatarsophalangeal joint;

CMC: Carpometacarpal Aletaha et al. Ann Rheum Dis 2010;69:1580-8.
 2010 ACR Classification Criteria for RA
• Serological categories ACPA and IgM-RF levels:

• Patients should be scored only if information from at least one serological test is available.
• The acute-phase response measures CRP or ESR are scored as normal or
abnormal based on the local laboratory standards.
• If results of at least one of these two tests are abnormal, the patient should be scored as
having an abnormal acute-phase response.
• Duration of symptoms: The patient’s self report of the maximum duration
of signs or symptoms of synovitis (pain, swelling, and tenderness) of any
joint that is clinically involved at the time of assessment (ie, the day the
criteria are applied).

IgM: Immunoglobulin M Aletaha et al. Ann Rheum Dis 2010;69:1580-8.

 Antibodies
Rheumatoid factor (RF) ACPA or Anti-CCP
Antibodies directed against the Fc portion of Anti-cyclic citrullinated peptide antibody 1-4
normal IgG1,2,4

Most often IgM but also IgG, IgA1-4 New group of autoantibodies1-4
Not specific of RA (71.6%) 1 Highly specificity for distinguishing RA from
other rheumatic diseases (90.4%) 3

75-80% of RA patients at some time during the The sensitivity of ACPA is 66.0%
course of their disease1

Seropositivity is more frequent than ACPA antibodies appear to be highly predictive

seronegativity1: of the future development of RA3
-Associated with aggressive form of the -In both healthy subjects and in patients
disease with undifferentiated arthritis
-Frequently complicated by rheumatoid
nodules and vasculitis

The presence of RF may antedate the clinical The presence of anti-CCP antibody is associated
development of RA2 with development of RA and greater
radiographic progression4
Differential Diagnosis
• Viral polyarthritis
• Other systemic rheumatic diseases, including SLE, Sjögren's
syndrome, DM, overlap syndromes such as mixed connective
tissue disease.
• Palindromic rheumatism
• Osteoarthritis
• Reactive arthritis and arthritis of inflammatory bowel disease
• Psoriatic arthritis
• Polymyalgia rheumatica
• Crystalline arthritis
• Hypermobility syndrome and fibromyalgia
• Paraneoplastic and cancer treatment-related disease
Extra-articular Manifestations
Disease Activity Score DAS-28
Management Goals in Rheumatoid Arthritis
• Classical objectives1
• Reduce disease activity
• Decrease disability
• Delay/prevent structural damage
• Current goals2-4
• Suppression of inflammation and control of comorbidities and
complications2
• Achieve persistent, total disease suppression resulting in remission.
Remission will halt damage, prevent disability, improve quality of life,
and lower mortality rates3
• Clinical management goals include enabling rapid access to optimum
diagnosis and care and the well-informed use of multiple treatments
approved for this disease4
Non-Pharmacologic Management of RA
• Joint-specific dynamic exercises
• Occupational therapy
• Hydrotherapy
• Psychological counselling
Other aspects of overall RA patient care include:
• Smoking cessation
• Weight control
• Vaccination
• Management of comorbidities
• Dental care
Adapted from Combe B et al. Ann Rheum Dis 2017;76:948-59.
Glucocorticoids
 Short term glucocorticoids should be
considered when initiating or changing
csDMARD therapy1,2
• Bridge therapy while waiting for DMARD
therapy to take effect
• Symptom control if no other options exist
 Glucocorticoids should be used in the lowest
possible dose and tapered as soon as
clinically possible2
1. Smolen JS, et al. Ann Rheum Dis. 2020;79:685-99 2. Hua et al. RMD Open 2020;6:e000536.

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